This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acek is a bifunctional kinase and phosphatase, which regulates isocitrate dehydrogenase (IDH) involved in a bypass of Krebs? cycle. This was the first phosphorylation system to be identified in bacteria, and is one of the only two known Ser/Thr phosphorylation systems. AceK may possess a novel structural fold and the structure of Acek may reveal the structural basis of molecular switch between kinase and phosphatase within a single protein. Furthermore, we have recently obtained a complex crystal between Acek and IDH, which may well be the first kinase complex structure with protein substrate. This complex structure will shed new lights on the substrate recognition and activity regulation.